There exists a large group of acute and chronic neuropsychiatric disorders for which safe and clinically effective treatments are not currently available. This diverse group of disorders encompasses a broad spectrum of initial events which are characterised by the initiation of progressive processes that sooner or later lead to neuronal cell death and dysfunction. Stroke, cerebral ischaemia, trauma or a neurodegenerative disease such as Alzheimer's disease or Parkinson's disease are all commonly occurring conditions that are associated with neurodegeneration of the brain and/or spinal cord.
The ongoing search for potential treatments of neurodegenerative disorders has involved investigation of excitatory amino acid antagonists, inhibitors of lipid peroxidation, calcium channel antagonists, inhibitors of specific pathways of the arachidonic acid cascade, kappa opioid agonists, adenosine agonists, PAF antagonists and diverse other agents. At the present time there is no consensus of the relative importance of the role played by compounds belonging to any of these general classes.
In a series of papers concerned with the chemistry of pyrrole dyes, A. Treibs and co-workers (Leibig's Ann. Chem., 1957, 602, 153-183 and 1958, 612, 242-264) have characterised a number of 1,1-dipyrrole alkenes of the following formula: ##STR2## In a paper on the reactions of fulvenes with 1,3-dipolar compounds (Leibig's Ann. Chem., 1981, 491-501), the following compound is disclosed: ##STR3## No pharmacological activity is associated with any of the above compounds. The substitution pattern of the above compounds places them outside the scope of the present invention.
European patent application EP 293220 and J. Heterocyclic
Chem., 1990, 27, 1933-40 disclose 1,5-diaryl pyrazoles of formula: ##STR4##
Said compounds are related to possible anti-inflammatory agents. Such activity requires the presence of the 1,5-diaryl substituents, a feature which excludes these compounds from the scope of the present invention.
In patent application EP 351 194 compounds of the general formula: ##STR5## wherein Q is thiazolyl, Ar.sup.1 is aryl of up to 10 carbon atoms, Ar.sup.2 is 6-membered aryl, including pyridyl, X is 0, S, SO, SO.sub.2 or NH and A is a direct link to X or is (1-6C)alkylene, (3-6C)alkenylene, (3-6C)alkynylene or cyclo(3-6C)alkylene are disclosed as 5-lipoxygenase inhibitors. The substituent Ar.sup.1 -A-X is not included within the scope of R.sup.1 in claim 1 of the present invention.
Monatsh. Chem. 1987, 118, 1031-1038, discloses a compound of formula: ##STR6## and J. Heterocyclic Chem., 1989, 26, 1869-1873 describes compounds of formulae ##STR7## No pharmacological activity is associated with the compounds in either of these two papers. These three specific compounds are deleted from the scope of the present invention by a disclaimer in claim 1.
In Zh. Obshch. Khim., 1962, 32, 2664-2670 (Chem. Abs. 58: 9057h), 1-(4-pyridyl)-1-(2-thiazolyl)ethanol is described. In Zh. Obshch. Khim., 1963, 33, 825-828 (Chem.Abs. 59: 8722a), 1-(2-pyridyl)-1-(2-thiazolyl)ethanol is described. No pharmacological activity is associated with either of these two compounds. These two specific compounds are deleted from the scope of the present invention by a disclaimer in claim 1.